論文 - 詳細
| RRC ID | 42254 |
|---|---|
| 著者 | Onuma E, Sato K, Saito H, Tsunenari T, Ishii K, Esaki K, Yabuta N, Wakahara Y, Yamada-Okabe H, Ogata E. |
| タイトル | Generation of a humanized monoclonal antibody against human parathyroid hormone-related protein and its efficacy against humoral hypercalcemia of malignancy. |
| ジャーナル | Anticancer Res |
| Abstract |
A humanized monoclonal antibody against parathyroid hormone-related protein (PTHrP) was generated from the mouse monoclonal antibody raised against the peptide corresponding to the N-terminal 34 amino acids of the human PTHrP [(PTHrP(1-34)]. The humanized antibody interacted with the PTHrP(1-34) with a kD value of 1.90 x 10(-10) M, and the epitope resides between the amino acids 20 and 30 of the PTHrP. PTHrP(1-34) significantly increased the intracellular cAMP levels in the rat osteosarcoma cells that expressed PTHR1, and the 5 microg/mL or higher concentrations of the humanized antibody almost completely blocked the PTHrP-induced cAMP production even in the presence of 2 microg/mL PTHrP(1-34), demonstrating its ability to fully neutralize PTHrP function. There was no significant difference in the potency of the mouse, chimera, or the humanized antibodies to suppress the PTHrP-induced increase in the intracellular cAMP in ROS cells. Furthermore, at the same doses, the administration of the chimera or the humanized antibody was equally effective in reducing the blood ionized calcium levels of hypercalcemic mice bearing the PAN-7-JCK human pancreatic cancer xenograft or the LC-6-JCK human lung cancer xenograft that secreted PTHrP. Thus, humanized anti-PTHrP may be useful for the treatment of the humoral hypercalcemia of malignancy in humans. |
| 巻・号 | 24(5A) |
| ページ | 2665-73 |
| 公開日 | 2004-1-1 |
| PMID | 15517871 |
| MeSH | Amino Acid Sequence Animals Antibodies, Monoclonal / biosynthesis Antibodies, Monoclonal / genetics Antibodies, Monoclonal / immunology* Antibodies, Monoclonal / pharmacology* Cell Line, Tumor Humans Hypercalcemia / blood Hypercalcemia / etiology Hypercalcemia / therapy* Immunoglobulin Heavy Chains / genetics Immunoglobulin Light Chains / genetics Lung Neoplasms / blood Lung Neoplasms / complications Male Mice Mice, Inbred BALB C Mice, Nude Molecular Sequence Data Pancreatic Neoplasms / blood Pancreatic Neoplasms / complications Parathyroid Hormone-Related Protein / antagonists & inhibitors* Parathyroid Hormone-Related Protein / immunology* Peptide Fragments / immunology* Rats Rats, Inbred F344 Rats, Nude Recombinant Fusion Proteins / biosynthesis Recombinant Fusion Proteins / genetics Recombinant Fusion Proteins / immunology Recombinant Fusion Proteins / pharmacology Xenograft Model Antitumor Assays |
| IF | 1.994 |
| 引用数 | 27 |
| WOS 分野 | ONCOLOGY |
| オルトメトリクス指標 |
オルトメトリクス指標項目
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| 最多言及媒体 | Patent(IFI CLAIMS) |
| 各媒体での言及数の合計 | 13 |
| 過去6か月間でのオルトメトリクス指標の変動値 | 0.0 |
| リソース情報 | |
| ヒト・動物細胞 | ROS-17/2.8-5(RCB0462) |